RU2009149214A - COMPOUNDS SUITABLE FOR APPLICATION AS RAF KINASE INHIBITORS - Google Patents

COMPOUNDS SUITABLE FOR APPLICATION AS RAF KINASE INHIBITORS Download PDF

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Publication number
RU2009149214A
RU2009149214A RU2009149214/04A RU2009149214A RU2009149214A RU 2009149214 A RU2009149214 A RU 2009149214A RU 2009149214/04 A RU2009149214/04 A RU 2009149214/04A RU 2009149214 A RU2009149214 A RU 2009149214A RU 2009149214 A RU2009149214 A RU 2009149214A
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RU
Russia
Prior art keywords
compound
possibly substituted
formula
nitrogen
independently selected
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RU2009149214/04A
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Russian (ru)
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RU2492166C2 (en
Inventor
Вэйжун ЧЭНЬ (US)
Вэйжун ЧЭНЬ
Дженнифер КОССРОУ (US)
Дженнифер КОССРОУ
Ллойд ФРАНКЛИН (US)
Ллойд Франклин
Бин ГУАНЬ (US)
Бин ГУАНЬ
Джон Ховард ДЖОУНЗ (US)
Джон Ховард ДЖОУНЗ
Гнанасамбандам КУМАРАВЕЛ (US)
Гнанасамбандам Кумаравел
Бенджамин ЛЭЙН (US)
Бенджамин ЛЭЙН
Адам ЛИТТКЕ (US)
Адам ЛИТТКЕ
Алексей ЛУГОВСКОЙ (US)
Алексей Луговской
Хайжо ПЭН (US)
Хайжо ПЭН
Ноэль ПАУЭЛЛ (US)
Ноэль ПАУЭЛЛ
Брайан РАЙМУНДО (US)
Брайан РАЙМУНДО
Хироко ТАНАКА (US)
Хироко Танака
Джеффри ВЕССЕЛЗ (US)
Джеффри ВЕССЕЛЗ
Томас УИНН (US)
Томас УИНН
Чжили СИНЬ (US)
Чжили СИНЬ
Original Assignee
Санесис Фармасьютикалз, Инк. (Us)
Санесис Фармасьютикалз, Инк.
Байоджен Айдек Ма Инк. (Us)
Байоджен Айдек Ма Инк.
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Application filed by Санесис Фармасьютикалз, Инк. (Us), Санесис Фармасьютикалз, Инк., Байоджен Айдек Ма Инк. (Us), Байоджен Айдек Ма Инк. filed Critical Санесис Фармасьютикалз, Инк. (Us)
Publication of RU2009149214A publication Critical patent/RU2009149214A/en
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Publication of RU2492166C2 publication Critical patent/RU2492166C2/en

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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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Abstract

1. Соединение формулы I: ! ! или фармацевтические приемлемая соль указанного соединения, где: ! Су1 представляет собой возможно замещенный фенил или возможно замещенное 5-6-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы; !Су2 представляет собой возможно замещенный 5-14-членное насыщенное, частично ненасыщенное или ароматическое моноциклическое, бициклическое или трициклическое кольцо, содержащее от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы; ! L1 представляет собой прямую связь или возможно замещенную линейную или разветвленную алкиленовую цепь C1-6; ! L2 представляет собой прямую связь или возможно замещенную линейную или разветвленную алкиленовую цепь C1-6, при этом один или два метиленовых звена в группе L2 могут быть независимо замещены на -O-, -S-, -N(R)-, -C(O)-, -C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -OC(O)-, -C(O)O- или 3-6-членный циклоалкилен; ! каждая группа R независимо представляет собой водород или возможно замещенную алифатическую группу C1-6; ! R1 представляет собой водород или возможно замещенную алифатическую группу C1-6; ! каждый из Rx и Ry независимо выбран из следующих групп: -R2, -галоген, -NO2, -CN, -OR2, -SR2, -N(R2)2, -C(O)R2, -CO2R2, -C(O)C(O)R2, -C(O)CH2C(O)R2, -S(O)R2, -S(O)2R2, -C(O)N(R2)2, -SO2N(R2)2, -OC(O)R2, -N(R2)C(O)R2, -N(R2)N(R2)2, -N(R2)-C(=NR2)N(R2)2, -C(=NR2)N(R2)2, -C=NOR2, -N(R2)C(O)N(R2)2, -N(R2)SO2N(R2)2, -N(R2)SO2R2 или -OC(O)N(R2)2; и ! каждый R2 независимо представляет собой водород или возможно замещенную группу, выбранную из следующих групп: алифатической C1-6, моноциклического или бициклического арильного кольца С6-10 или 5-10-членного насыщенного, частично ненасыщенного или ар 1. The compound of formula I:! ! or a pharmaceutical acceptable salt of said compound, wherein:! Cy1 represents a possibly substituted phenyl or a possibly substituted 5-6 membered saturated, partially unsaturated or aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; ! Cy2 is a possibly substituted 5-14 membered saturated, partially unsaturated or aromatic monocyclic, bicyclic or tricyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur; ! L1 represents a direct bond or optionally substituted linear or branched alkylene chain C1-6; ! L2 represents a direct bond or a possibly substituted linear or branched alkylene chain C1-6, while one or two methylene units in the group L2 can be independently replaced by -O-, -S-, -N (R) -, -C ( O) -, -C (O) N (R) -, -N (R) C (O) N (R) -, -N (R) C (O) -, -N (R) C (O) O-, -OC (O) N (R) -, -SO2-, -SO2N (R) -, -N (R) SO2-, -OC (O) -, -C (O) O- or 3- 6 membered cycloalkylene; ! each R group independently represents hydrogen or a possibly substituted aliphatic C1-6 group; ! R1 represents hydrogen or a possibly substituted aliphatic group C1-6; ! each of Rx and Ry is independently selected from the following groups: -R2, -halogen, -NO2, -CN, -OR2, -SR2, -N (R2) 2, -C (O) R2, -CO2R2, -C (O ) C (O) R2, -C (O) CH2C (O) R2, -S (O) R2, -S (O) 2R2, -C (O) N (R2) 2, -SO2N (R2) 2, -OC (O) R2, -N (R2) C (O) R2, -N (R2) N (R2) 2, -N (R2) -C (= NR2) N (R2) 2, -C (= NR2) N (R2) 2, -C = NOR2, -N (R2) C (O) N (R2) 2, -N (R2) SO2N (R2) 2, -N (R2) SO2R2 or -OC (O ) N (R2) 2; and! each R2 independently represents hydrogen or a possibly substituted group selected from the following groups: aliphatic C1-6, monocyclic or bicyclic aryl rings C6-10 or 5-10 membered saturated, partially unsaturated or ar

Claims (38)

1. Соединение формулы I:1. The compound of formula I:
Figure 00000001
Figure 00000001
 или фармацевтические приемлемая соль указанного соединения, где:or a pharmaceutically acceptable salt of said compound, wherein: Су1 представляет собой возможно замещенный фенил или возможно замещенное 5-6-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы;Su 1 represents a possibly substituted phenyl or a possibly substituted 5-6 membered saturated, partially unsaturated or aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; Су2 представляет собой возможно замещенный 5-14-членное насыщенное, частично ненасыщенное или ароматическое моноциклическое, бициклическое или трициклическое кольцо, содержащее от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы;Su 2 is a possibly substituted 5-14 membered saturated, partially unsaturated or aromatic monocyclic, bicyclic or tricyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur; L1 представляет собой прямую связь или возможно замещенную линейную или разветвленную алкиленовую цепь C1-6;L 1 represents a direct bond or optionally substituted linear or branched alkylene chain C 1-6 ; L2 представляет собой прямую связь или возможно замещенную линейную или разветвленную алкиленовую цепь C1-6, при этом один или два метиленовых звена в группе L2 могут быть независимо замещены на -O-, -S-, -N(R)-, -C(O)-, -C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -OC(O)-, -C(O)O- или 3-6-членный циклоалкилен;L 2 represents a direct bond or a possibly substituted linear or branched alkylene chain C 1-6 , while one or two methylene units in the group L 2 can be independently substituted by -O-, -S-, -N (R) -, -C (O) -, -C (O) N (R) -, -N (R) C (O) N (R) -, -N (R) C (O) -, -N (R) C (O) O-, -OC (O) N (R) -, -SO 2 -, -SO 2 N (R) -, -N (R) SO 2 -, -OC (O) -, -C ( O) O- or 3-6 membered cycloalkylene; каждая группа R независимо представляет собой водород или возможно замещенную алифатическую группу C1-6;each R group independently represents hydrogen or a possibly substituted aliphatic group C 1-6 ; R1 представляет собой водород или возможно замещенную алифатическую группу C1-6;R 1 represents hydrogen or a possibly substituted aliphatic group of C 1-6 ; каждый из Rx и Ry независимо выбран из следующих групп: -R2, -галоген, -NO2, -CN, -OR2, -SR2, -N(R2)2, -C(O)R2, -CO2R2, -C(O)C(O)R2, -C(O)CH2C(O)R2, -S(O)R2, -S(O)2R2, -C(O)N(R2)2, -SO2N(R2)2, -OC(O)R2, -N(R2)C(O)R2, -N(R2)N(R2)2, -N(R2)-C(=NR2)N(R2)2, -C(=NR2)N(R2)2, -C=NOR2, -N(R2)C(O)N(R2)2, -N(R2)SO2N(R2)2, -N(R2)SO2R2 или -OC(O)N(R2)2; иeach of R x and R y is independently selected from the following groups: —R 2 , —halogen, —NO 2 , —CN, —OR 2 , —SR 2 , —N (R 2 ) 2 , —C (O) R 2 , -CO 2 R 2 , -C (O) C (O) R 2 , -C (O) CH 2 C (O) R 2 , -S (O) R 2 , -S (O) 2 R 2 , -C (O) N (R 2 ) 2 , -SO 2 N (R 2 ) 2 , -OC (O) R 2 , -N (R 2 ) C (O) R 2 , -N (R 2 ) N (R 2 ) 2 , -N (R 2 ) -C (= NR 2 ) N (R 2 ) 2 , -C (= NR 2 ) N (R 2 ) 2 , -C = NOR 2 , -N (R 2 ) C (O) N (R 2 ) 2 , -N (R 2 ) SO 2 N (R 2 ) 2 , -N (R 2 ) SO 2 R 2 or -OC (O) N (R 2 ) 2 ; and каждый R2 независимо представляет собой водород или возможно замещенную группу, выбранную из следующих групп: алифатической C1-6, моноциклического или бициклического арильного кольца С6-10 или 5-10-членного насыщенного, частично ненасыщенного или ароматического моноциклического или бициклического кольца, содержащего от 1 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы, илиeach R 2 independently represents hydrogen or a possibly substituted group selected from the following groups: aliphatic C 1-6 , monocyclic or bicyclic aryl ring, C 6-10 or 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring from 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or две группы R2 у одного и того же атома азота совместно с указанным атомом азота образуют возможно замещенное 5-8-членный насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы.two R 2 groups on the same nitrogen atom together with the specified nitrogen atom form a possibly substituted 5-8 membered saturated, partially unsaturated or aromatic ring containing from 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur. 2. Соединение по п.1, в котором каждый из Rx и Ry независимо выбран из следующих групп: R2, галоген. -OR2, -N(R2)2, -OC(O)R2, -N(R2)C(O)R2, -N(R2)N(R2)2, -N(R2)C(O)N(R2)2, -N(R2)SO2N(R2)2, -N(R2)SO2R2 или -OC(O)N(R2)2.2. The compound according to claim 1, in which each of R x and R y independently selected from the following groups: R 2 , halogen. -OR 2 , -N (R 2 ) 2 , -OC (O) R 2 , -N (R 2 ) C (O) R 2 , -N (R 2 ) N (R 2 ) 2 , -N (R 2 ) C (O) N (R 2 ) 2 , -N (R 2 ) SO 2 N (R 2 ) 2 , -N (R 2 ) SO 2 R 2 or -OC (O) N (R 2 ) 2 . 3. Соединение по п.2, в котором Rx представляет собой водород, возможно замещенную алифатическую группу C1-6 или галоген.3. The compound according to claim 2, in which R x represents hydrogen, a possibly substituted aliphatic group C 1-6 or halogen. 4. Соединение по п.2, в котором группа Ry выбрана из R2, -OR2 или -N(R2)2.4. The compound according to claim 2, in which the group R y selected from R 2 , -OR 2 or -N (R 2 ) 2 . 5. Соединение по п.4, в котором Ry представляет собой -NH2, -NHCH3, -NHCH2CH3, -NHCH2CH2CH3, -NHCH(CH3)2, -NH(С3Н5), -NHCH2CH2CH2OH, -N(CH2CH2)2O или -NHCH2CH2CH2NH(CH3)2.5. The compound according to claim 4, in which R y represents —NH 2 , —NHCH 3 , —NHCH 2 CH 3 , —NHCH 2 CH 2 CH 3 , —NHCH (CH 3 ) 2 , —NH (C 3 H 5 ), —NHCH 2 CH 2 CH 2 OH, —N (CH 2 CH 2 ) 2 O, or —NHCH 2 CH 2 CH 2 NH (CH 3 ) 2 . 6. Соединение по п.4, в котором Ry представляет собой возможно замещенную алифатическую группу C1-6.6. The compound according to claim 4, in which R y represents a possibly substituted aliphatic group C 1-6 . 7. Соединение по п.6, в котором Ry представляет собой возможно замещенную группу, выбранную из С2-6алкенильной или С2-6алкинильной группы.7. The compound according to claim 6, in which R y represents a possibly substituted group selected from a C 2-6 alkenyl or C 2-6 alkynyl group. 8. Соединение по п.4, в котором Ry представляет собой возможно замещенное 5-10-членное насыщенное моноциклическое или бициклическое кольцо, содержащее от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы.8. The compound according to claim 4, in which R y represents a possibly substituted 5-10 membered saturated monocyclic or bicyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur. 9. Соединение по п.8, в котором Ry представляет собой возможно замещенную группу, выбранную из:9. The compound of claim 8, in which R y represents a possibly substituted group selected from: (a) 5-6-членното насыщенного моноциклического кольца, содержащего от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы;(a) a 5-6 membered saturated monocyclic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; (b) 5-6-членного ароматического кольца, содержащего от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы; или(b) a 5-6 membered aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; or (c) 8-10-членного насыщенного, частично ненасыщенного или ароматического бициклического кольца, содержащего от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы.(c) an 8-10 membered saturated, partially unsaturated or aromatic bicyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur. 10. Соединение по п.8, в котором Ry представляет собой возможно замещенную группу, выбранную фенила, октагидроазоцинила, тиоциклопентанила, тиоциклогексанила, пирролидинила, пиперидинила, пиперазинила, тетрагидротиопиранила, тетрагидротиофенила, дитиоланила, тетрагидрофуранила, тетрагидропиранила, диоксанила, тиоксанила, морфолинила, оксатиоланила, имидазолидинила, пирролила, пиразолила, имидазолила, триазолила, тетразолила, тиофенила, фуранила, тиазолила, изотиазолила, тиадиазолила, оксазолила, изоксазолила, оксадиазолила, пиридинила, пиримидинила, пиразинила, пиридазинила, триазинила, тетразинила, тетрагидропиридинила, бензофуранила, тианафтенила, пиролизинила, индолила, хинолинила, изохинолинила, бензимидазолила, имидазопиридинила, пуринила, индазолила, пирролопиридинила, циннолинила, хиназолинила, фталазинила, нафтиридинила или хиноксалинила.10. The compound of claim 8, in which R y represents an optionally substituted group selected by phenyl, octahydroazocinyl, thiocyclopentanyl, thiocyclohexanyl, pyrrolidinyl, piperidinyl, piperazinyl, tetrahydrothiopyranyl, tetrahydrothiophenyl, tetrahydro-ynanyril, tetrahydro-ynopyrnyl, tetrahydro-ynanopyrnyl, tetrahydro-ynanopyrnyl, tetrahydro-ynopyrnyl, tetrahydro-ynopyrnyl, tetrahydro-ynanopyrnyl, tetrahydro-ynanopyrnyl, tetrahydro-ynanopyrnyl, tetrahydro-ynanopyril, , imidazolidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiophenyl, furanyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, tetrahydropyridinyl, benzofuranyl, tianaphthenyl, pyrolysinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, imidazopyridinyl, quinolinyl, quinolinyl, quinolinyl 11. Соединение по п.1, в котором R1 представляет собой водород, a L1 представляет собой возможно замещенную линейную или разветвленную алкиленовую цепь C1-4.11. The compound according to claim 1, in which R 1 represents hydrogen, and L 1 represents a possibly substituted linear or branched alkylene chain C 1-4 . 12. Соединение по п.11, в котором L1 представляет собой возможно замещенную разветвленную алкиленовую цепь C1-4.12. The compound according to claim 11, in which L 1 represents a possibly substituted branched alkylene chain C 1-4 . 13. Соединение по п.1, в котором Су1 представляет собой возможно замещенное 5-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы.13. The compound according to claim 1, in which Su 1 represents a possibly substituted 5-membered saturated, partially unsaturated or aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur. 14. Соединение по п.13, в котором Су1 представляет собой возможно замещенную пирролильную, пиразолильную, имидазолильную, триазолильную, тетразолильную, тиофенильную, фуранильную, тиазолильную, изотиазолильную, тиадиазолильную, оксазолильную, изоксазолильную или оксадиазолильную группу.14. The compound of claim 13, wherein Cy 1 is a possibly substituted pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiophenyl, furanyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl or oxadiazolyl group. 15. Соединение по п.1, в котором L2 представляет собой прямую связь или возможно замещенную линейную или разветвленную алкиленовую цепь C1-4, при этом один или два метиленовых звена в группе L2 замещены на -O-, -S-, -N(R)-, -C(O)-, -C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -ОС(O)- или -С(O)O-.15. The compound according to claim 1, in which L 2 represents a direct bond or a possibly substituted linear or branched alkylene chain C 1-4 , while one or two methylene units in the group L 2 are replaced by -O-, -S-, -N (R) -, -C (O) -, -C (O) N (R) -, -N (R) C (O) N (R) -, -N (R) C (O) - , -N (R) C (O) O-, -OC (O) N (R) -, -SO 2 -, -SO 2 N (R) -, -N (R) SO 2 -, -ОС ( O) - or -C (O) O-. 16. Соединение по п.15, в котором L2 представляет собой -C(O)N(R)-, -N(R)C(O)-, -SO2N(R)-, -N(R)SO2-, -OC(O)- или -C(O)O-.16. The compound of claim 15, wherein L 2 is —C (O) N (R) -, —N (R) C (O) -, —SO 2 N (R) -, —N (R) SO 2 -, -OC (O) - or -C (O) O-. 17. Соединение по п.16, в котором L2 представляет собой -C(O)N(H)- или -N(H)C(O)-.17. The compound of claim 16, wherein L 2 is —C (O) N (H) - or —N (H) C (O) -. 18. Соединение по п.1, в котором Су2 представляет собой возможно замещенную группу, выбранную из:18. The compound according to claim 1, in which Su 2 represents a possibly substituted group selected from: (a) 5-членного насыщенного, частично ненасыщенного или ароматического моноциклического кольца, содержащего от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы;(a) a 5-membered saturated, partially unsaturated or aromatic monocyclic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; (b) фенила или 6-членного насыщенного, частично ненасыщенного или ароматического моноциклического кольца, содержащего от 1 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы; или(b) phenyl or a 6-membered saturated, partially unsaturated or aromatic monocyclic ring containing from 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur; or (c) 5-10-членного насыщенного, частично ненасыщенного или ароматического бициклического кольца, содержащего от 1 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы.(c) a 5-10 membered saturated, partially unsaturated or aromatic bicyclic ring containing from 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur. 19. Соединение по п.18, в котором Су2 представляет собой возможно замещенную группу, выбранную из;19. The compound according to p. 18, in which Su 2 represents a possibly substituted group selected from; (a) 5-членного гетероарильного кольца, содержащего от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы;(a) a 5-membered heteroaryl ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; (b) фенила или 6-членного гетероарильного кольца, содержащего от 1 до 3 атомов азота; или(b) phenyl or a 6-membered heteroaryl ring containing from 1 to 3 nitrogen atoms; or (с) 5,6-конденсированного бициклического гетероарильного цикла, содержащего от 1 до 4 гетероатомов, выбранных из азота, кислорода или серы.(c) a 5,6-fused bicyclic heteroaryl ring containing from 1 to 4 heteroatoms selected from nitrogen, oxygen or sulfur. 20. Соединение по п.19, в котором Су2 представляет собой возможно замещенную группу, выбранную из фенила, пирролила, пиразолила, имидазолила, триазолила, тетразолила, тиофенила, фуранила, тиазолила, изотиазолила, тиадиазолила, оксазолила, изоксазолила, оксадиазолила, пиридинила, пиримидинила, пиразинила, пиридазинила, триазинила, тетразинила, пиролизинила, индолила, хинолинила, изохинолинила, бензимидазолила, имидазопиридинила, индазолила, пуринила, циннолинила, хиназолинила, фталазинила, нафтридинила, хиноксалинила, тианафтенила или бензофуранила.20. The compound according to claim 19, in which Su 2 represents a possibly substituted group selected from phenyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiophenyl, furanyl, thiazolyl, isothiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, pyridinyl pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, tetrazinyl, pyrolysinyl, indolyl, quinolinyl, isoquinolinyl, benzimidazolyl, imidazopyridinyl, indazolyl, purinyl, cinnolinyl, quinazolinyl, phthalazinyl, thienofenyl, or naphthinyl, furanyl. 21. Соединение по п.1, отличающееся тем, что указанное соединение представляет собой соединение формулы II:21. The compound according to claim 1, characterized in that the said compound is a compound of formula II:
Figure 00000002
Figure 00000002
 или фармацевтически приемлемую соль указанного соединения.or a pharmaceutically acceptable salt of said compound. 22. Соединение по п.22, отличающееся тем, что указанное соединение представляет собой соединение формулы II-а или II-b:22. The compound of claim 22, wherein said compound is a compound of formula II-a or II-b:
Figure 00000003
Figure 00000004
Figure 00000003
Figure 00000004
 23. Соединение по п.22, в котором Су1 представляет собой 5-членное гетероарильное кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы.23. The compound according to item 22, in which Su 1 represents a 5-membered heteroaryl ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur. 24. Соединение по п.1, отличающееся тем, что указанное соединение выбрано из соединений, представленных в Таблице 3, Таблице 4 или Таблице 5, или из фармацевтически приемлемых солей указанных соединений.24. The compound according to claim 1, characterized in that the said compound is selected from compounds shown in Table 3, Table 4 or Table 5, or from pharmaceutically acceptable salts of these compounds. 25. Фармацевтическая композиция, содержащая соединение по п.1 и фармацевтически приемлемый носитель, адъювант или наполнитель.25. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant or excipient. 26. Композиция по п.25 в комбинации с терапевтическим агентом, выбранным из химиотерапевтического или антипролиферативного агента, противовоспалительного агента, иммуномодулирующего агента, нейротрофического фактора, агента для лечения сердечно-сосудистого заболевания, агента для лечения деструктивных поражений костей, агента для лечения заболевания печени, противовирусного средства, агента для лечения нарушений крови, агента для лечения диабета или агента для лечения иммунодефицитных нарушений.26. The composition of claim 25 in combination with a therapeutic agent selected from a chemotherapeutic or antiproliferative agent, an anti-inflammatory agent, an immunomodulatory agent, a neurotrophic factor, an agent for treating cardiovascular disease, an agent for treating destructive bone lesions, an agent for treating liver disease, an antiviral agent, an agent for treating blood disorders, an agent for treating diabetes, or an agent for treating immunodeficiency disorders. 27. Способ ингибирования активности киназы Raf у пациента или в биологическом образце, включающий введение указанному пациенту соединения по п.1 или фармацевтической композиции указанного соединения, или приведение указанного биологического образца в контакт с соединением по п.1 или фармацевтической композицией указанного соединения.27. A method of inhibiting Raf kinase activity in a patient or in a biological sample, comprising administering to a specified patient a compound of claim 1 or a pharmaceutical composition of said compound, or contacting said biological sample with a compound of claim 1 or a pharmaceutical composition of said compound. 28. Способ лечения или уменьшения тяжести нарушения, опосредуемого Raf, у млекопитающего, страдающего от такого нарушения, причем указанное нарушение выбрано из пролиферативного нарушения, нарушения сердечной деятельности, нейродегенеративного нарушения, аутоиммунного нарушения, состояния, связанного с трансплантацией органа, воспалительного нарушения, иммунологически опосредуемого нарушения, вирусного заболевания или поражения костей, при этом указанный способ включает этап введения указанному пациенту соединения по п.1 или фармацевтической композиции на основе указанного соединения.28. A method of treating or reducing the severity of a Raf-mediated disorder in a mammal suffering from such a disorder, said disorder being selected from a proliferative disorder, a cardiac disorder, a neurodegenerative disorder, an autoimmune disorder, an organ transplant related condition, an inflammatory disorder immunologically mediated disorders, viral diseases or bone damage, wherein said method comprises the step of administering to said patient a compound according to claim 1 or a pharmacist a chemical composition based on said compound. 29. Способ по п.28, в котором указанное нарушение выбрано из меланомы, лейкоза, рака толстой кишки, рака молочной железы, рака желудочно-кишечного тракта, рака яичников, рака легкого, рака головного мозга, рака гортани, рака шейки матки, рака почки, рака лимфатической системы, рака мочеполового тракта (включая рак мочевого пузыря и рак предстательной железы), рака желудка, рака кости, лимфомы, меланомы, глиомы, папиллярного рака щитовидной железы, нейробластомы и рака поджелудочной железы.29. The method of claim 28, wherein said disorder is selected from melanoma, leukemia, colon cancer, breast cancer, gastrointestinal cancer, ovarian cancer, lung cancer, brain cancer, laryngeal cancer, cervical cancer, cancer kidney, cancer of the lymphatic system, cancer of the genitourinary tract (including bladder cancer and prostate cancer), stomach cancer, bone cancer, lymphoma, melanoma, glioma, papillary thyroid cancer, neuroblastoma, and pancreatic cancer. 30. Способ по п.29, включающий дополнительный этап введения указанному пациенту дополнительного терапевтического агента, выбранного из химиотерапевтического или антипролиферативного агента, противовоспалительного агента, иммуномодулирующего агента, нейротрофического фактора, агента для лечения сердечно-сосудистого заболевания, агента для лечения деструктивных поражений костей, агента для лечения заболевания печени, противовирусного средства, агента для лечения нарушений крови, агента для лечения диабета или агента для лечения иммунодефицитных нарушений, при этом:30. The method according to clause 29, comprising the additional step of introducing to the specified patient an additional therapeutic agent selected from a chemotherapeutic or antiproliferative agent, an anti-inflammatory agent, an immunomodulating agent, a neurotrophic factor, an agent for treating cardiovascular disease, an agent for treating destructive lesions of bones, an agent for treating liver disease, an antiviral agent, an agent for treating blood disorders, an agent for treating diabetes, or an agent for treating an immune deficit violations, while: указанный дополнительный терапевтический агент подходит для лечения указанного заболевания, подвергаемого лечению; иsaid additional therapeutic agent is suitable for treating said disease being treated; and указанный дополнительный терапевтический агент вводят совместно с указанной композицией в виде единой дозированной формы или отдельно от указанной композиции в виде части составной дозированной формы.the specified additional therapeutic agent is administered together with the specified composition in the form of a single dosage form or separately from the specified composition as a part of a composite dosage form. 31. Способ получения соединения формулы II-а':31. A method of obtaining a compound of formula II-a ':
Figure 00000005
Figure 00000005
 или фармацевтически приемлемой соли указанного соединения, где:or a pharmaceutically acceptable salt of said compound, wherein: Су1 представляет собой возможно замещенное 5-6-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы;Su 1 is a possibly substituted 5-6 membered saturated, partially unsaturated or aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; Су2 представляет собой возможно замещенное 5-10-членное насыщенное, частично ненасыщенное или ароматическое моноциклическое или бициклическое кольцо, содержащее от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы;Su 2 represents a possibly substituted 5-10 membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur; каждая из групп Rx и Ry независимо выбрана из -R2, -галогена, -NO2, -CN, -OR2, -SR2, -N(R2)2, -C(O)R2, -CO2R2, -C(O)C(O)R2, -C(O)CH2C(O)R2, -S(O)R2, -S(O)2R2, -C(O)N(R2)2, -SO2N(R2)2, -OC(O)R2, -N(R2)C(O)R2, -N(R2)N(R2)2, -N(R2)-C(=NR2)N(R2)2, -C(=NR2)N(R2)2, -C=NOR2, -N(R2)C(O)N(R2)2, -N(R2)SO2N(R2)2, -N(R2)SO2R2 или -OC(O)N(R2)2;each of the groups R x and R y is independently selected from -R 2 , -halogen, -NO 2 , -CN, -OR 2 , -SR 2 , -N (R 2 ) 2 , -C (O) R 2 , - CO 2 R 2 , -C (O) C (O) R 2 , -C (O) CH 2 C (O) R 2 , -S (O) R 2 , -S (O) 2 R 2 , -C (O) N (R 2 ) 2 , -SO 2 N (R 2 ) 2 , -OC (O) R 2 , -N (R 2 ) C (O) R 2 , -N (R 2 ) N (R 2 ) 2 , -N (R 2 ) -C (= NR 2 ) N (R 2 ) 2 , -C (= NR 2 ) N (R 2 ) 2 , -C = NOR 2 , -N (R 2 ) C (O) N (R 2 ) 2 , —N (R 2 ) SO 2 N (R 2 ) 2 , —N (R 2 ) SO 2 R 2, or —OC (O) N (R 2 ) 2 ; каждая группа R2 независимо представляет собой водород или возможно замещенную группу, выбранную из следующих групп: алифатической группы C1-6, моноциклического или бициклического арильного кольца С6-10 или 5-10-членного насыщенного, частично ненасыщенного или ароматического моноциклического или бициклического кольца, содержащего от 1 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы, илиeach R 2 group independently represents hydrogen or a possibly substituted group selected from the following groups: an aliphatic group C 1-6 , a monocyclic or bicyclic aryl ring, a C 6-10 or 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring containing from 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or две группы R2 у одного и того же атома азота совместно с указанным атомом азота образуют возможно замещенное 5-8-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы,two R 2 groups on the same nitrogen atom together with the specified nitrogen atom form a possibly substituted 5-8 membered saturated, partially unsaturated or aromatic ring containing from 1 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, включающий стадию осуществления сочетания соединения формулы II- viii.comprising the step of coupling a compound of formula II-viii.
Figure 00000006
Figure 00000006
 с соединением формулы II-vii:with a compound of formula II-vii:
Figure 00000007
Figure 00000007
 с образованием соединения формулы II-а'.with the formation of the compounds of formula II-a '. 32. Способ по п.31, в котором соединение формулы II-vii получают из соединения формулы II-vi-b:32. The method according to p, in which the compound of formula II-vii is obtained from the compounds of formula II-vi-b:
Figure 00000008
Figure 00000008
 где А- представляет собой подходящий хиральный анион,where A is a suitable chiral anion, включающий стадию обработки соединения формулы II-vi-b подходящим основанием с образованием соединения формулы II-vii.comprising the step of treating a compound of formula II-vi-b with a suitable base to form a compound of formula II-vii. 33. Способ по п.32, в котором соединение формулы II-vi-b получают из соединения формулы II-v:33. The method according to p, in which the compound of formula II-vi-b is obtained from the compounds of formula II-v:
Figure 00000009
,
Figure 00000009
, включающий следующие стадии:comprising the following steps: (а) обработки соединения формулы II-v хиральным агентом с образованием соединения формулы II-vi-a:(a) treating the compound of formula II-v with a chiral agent to form a compound of formula II-vi-a:
Figure 00000010
Figure 00000010
 иand (b) разделения полученных диастереомеров с помощью подходящих физических способов с получением соединения формулы II-vi-b.(b) separating the resulting diastereomers using suitable physical methods to obtain a compound of formula II-vi-b. 34. Способ по п.33, в котором соединение формулы II-v:34. The method according to p, in which the compound of formula II-v:
Figure 00000011
Figure 00000011
 получают из соединения формулы II-iv,obtained from the compounds of formula II-iv, включающий стадию превращения оксимного фрагмента формулы II-iv в аминогруппу формулы II-v.comprising the step of converting an oxime moiety of formula II-iv to an amino group of formula II-v. 35. Способ по п.34, в котором соединение формулы II-iv получают из соединения формулы II-iii:35. The method according to clause 34, in which the compound of formula II-iv is obtained from the compounds of formula II-iii:
Figure 00000012
,
Figure 00000012
, включающий стадию обработки соединения формулы II-iii гидроксиламином с образованием соединения формулы II-iv.comprising the step of treating a compound of formula II-iii with hydroxylamine to form a compound of formula II-iv. 36. Способ по п.35, в котором соединение формулы II-iii получают путем осуществления сочетания соединения формулы II-i:36. The method according to clause 35, in which the compound of formula II-iii is obtained by combining a compound of formula II-i:
Figure 00000013
Figure 00000013
 с соединением формулы II-ii:with the compound of formula II-ii:
Figure 00000014
,
Figure 00000014
, 37. Соединение формулы II-vi-a или II-vi-b.37. The compound of formula II-vi-a or II-vi-b.
Figure 00000010
Figure 00000015
Figure 00000010
Figure 00000015
 в котором А- представляет собой подходящий хиральный анион,in which A - represents a suitable chiral anion, Су1 представляет собой возможно замещенное 5-6-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы; иSu 1 is a possibly substituted 5-6 membered saturated, partially unsaturated or aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; and Су2 представляет собой возможно замещенное 5-10-членное насыщенное, частично ненасыщенное или ароматическое моноциклическое или бициклическое кольцо, содержащее от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы.Su 2 is a possibly substituted 5-10 membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur. 38. Соединение формулы II-iv:38. The compound of formula II-iv:
Figure 00000016
,
Figure 00000016
, в котором Су1 представляет собой возможно замещенное 5-6-членное насыщенное, частично ненасыщенное или ароматическое кольцо, содержащее от 1 до 3 гетероатомов, независимо выбранных из азота, кислорода или серы; иin which Su 1 represents a possibly substituted 5-6 membered saturated, partially unsaturated or aromatic ring containing from 1 to 3 heteroatoms independently selected from nitrogen, oxygen or sulfur; and Су2 представляет собой возможно замещенное 5-10-членное насыщенное, частично ненасыщенное или ароматическое моноциклическое или бициклическое кольцо, содержащее от 0 до 4 гетероатомов, независимо выбранных из азота, кислорода или серы. Su 2 is a possibly substituted 5-10 membered saturated, partially unsaturated or aromatic monocyclic or bicyclic ring containing from 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur.
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